A liver disorder, hepatitis can be caused by viruses, alcohol and drugs. Of hepatitis of different etiology, viral hepatitis is most common. Viral hepatitis is caused by hepatitis viruses that infect the liver. In particular, hepatitis B and hepatitis C are known to lead not only to acute hepatic failure, but also to hepatic cirrhosis and liver cancer at a significantly high rate (Non-Patent Documents 1 and 2). Of the more than 40,000 deaths each year resulting from liver cancer and hepatic cirrhosis in Japan, approximately 70% are infected with hepatitis C virus and approximately 20% with hepatitis B virus (Non-Patent Document 3).
The therapeutic agents for hepatitis B and C have been intensively developed in recent years. However, even lamivudine, one of the most promising therapeutic agents for hepatitis B, is not effective to an extent that eliminates hepatitis B virus (HVB) from all of the patients (Non-Patent Document 4). Although the introduction of interferons (IFN) has brought about the recent advances in the treatment of hepatitis C, the combination therapy of IFN preparations and ribavirin is not effective enough (Non-Patent Document 5). Despite the progress of conventional therapeutic agents, many people persistently infected with the viruses are still in need of treatments since persistent hepatitis can lead to hepatic cirrhosis and, ultimately, to hepatic cell carcinoma.
Recently, viral hepatitis has been realized as a incomplete immunological interaction between the host and the viruses without viral elimination (Non-Patent Document 6). It is now believed that the viruses harm the liver cells not by directly damaging the liver cells, but as a result of immune responses in which host's immune cells such as cytotoxic T cells eliminate and destroy the infected liver cells. The ideal treatment for the viral hepatitis is of course the elimination of virus. As in hepatitis C, the viral load is not necessarily a function of the severity of inflammation in hepatitis B.
Asymptomatic HBV carriers do not have liver inflammation despite a high viral load. When elimination of the virus is impossible, another option is to keep patients in a state of asymptomatic HBV carrier in which the virus survives but does not cause inflammation. The present invention provides compounds that prevent the onset of liver inflammation by suppressing T-cell activation.
2-amino-1,3-propanediol derivatives described in the present application are already described compounds (Patent Documents 1 and 2) and are known to be useful as immunosuppressors. Nonetheless, there is no previous studies or reports that demonstrate their use against liver diseases or suggest their efficacy to suppress liver inflammation.    Non-Patent Document 1 Annu. Rev. Biochem. 56: 651 (1987)    Non-Patent Document 2 Proc. Natl. Acad. Sci. USA, 87: 6547 (1990)    Non-Patent Document 3 Sogo Rinsyo, 54: 449 (2005)    Non-Patent Document 4 N. Engl. J. Med., 348: 848 (2003)    Non-Patent Document 5 N. Engl. J. Med., 347: 975 (2002)    Non-Patent Document 6 J. Clin. Invest., 99: 1472 (1997)    Patent Document 1 WO 2003/029184 pamphlet    Patent Document 2 WO 2003/029205 pamphlet